1,4-Dibromobenzene → 2-(4-Bromophenyl)pyridine

Temperature

-78 °C

1,4-Dibromobenzene (5.90 g, 25.0 mmol) was dissolved in anhydrous diethyl ether (40 mL) and flushed with argon before the solution was cooled to −78° C. and n-butyl lithium (2.5M in hexanes, 10.2 mL, 25.6 mmol) was added dropwise at a rate that maintained the temperature below −70° C. The reaction mixture was stirred at this temperature for 30 minutes then 2-fluoropyridine (1.72 mL, 20.0 mmol) was added dropwise and stirring continued at −78° C. for 1 h then the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was poured onto water (50 mL) and extracted with diethyl ether (3×50 mL). The combined organic layers were washed with 5% HCl (3×200 mL) then the pH of the aqueous phase was adjusted to 10 by the addition of potassium hydroxide and the aqueous phase was extracted with diethyl ether (3×200 mL). The combined organic phase was dried over sodium sulfate, filtered and evaporated to afford the title compound (2.7 g, 58%). 1H NMR (CDCl3, 300 MHz): 8.71-8.66 (m, 1H), 7.91-7.85 (m, 2H), 7.79-7.67 (m, 2H), 7.64-7.57 (m, 2H), 7.28-7.22 (m, 1H).

1. customflushed with argon before the solution
2. temperaturemaintained the temperature below −70° C
3. stirringstirring
4. waitcontinued at −78° C. for 1 h
5. temperatureto warm to room temperature
6. stirringstirred for 1 h
7. additionThe reaction mixture was poured onto water (50 mL)
8. extractionextracted with diethyl ether (3×50 mL)
9. washThe combined organic layers were washed with 5% HCl (3×200 mL)
10. additionthe pH of the aqueous phase was adjusted to 10 by the addition of potassium hydroxide
11. extractionthe aqueous phase was extracted with diethyl ether (3×200 mL)
12. dry with materialThe combined organic phase was dried over sodium sulfate
13. filtrationfiltered
14. customevaporated

ORD record

ord-4c6a4148cf5e402aa4ef189d194c41a2

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501765B2